Many metabolites are prone to be damaged by either spontaneous in the forming step or enzymatic side reactions. Similar to the macromolecular repair, metabolic pathway also has a unique damage-control system in controlling level of damage byproducts. Metabolite damage-control systems are often widely distributed. Also, hundreds of enzymes are functionally unclear, many of which cannot belong to metabolite synthesis or degradation pathways and believed to be candidates of Metabolite damage-control systems. Comparative genomics can pick out candidates for new metabolite damage-control genes from the enzyme genes of unknown function by predicting a gene’s function from those of the genes that are associated with it. We are now collaborating with several research groups and identify some damage-control systems for metabolite repair.